Silicone foam compositions rapidly cross-linkable at ambient temperatures and methods of making and using same

ABSTRACT

Provided are rapidly cross-linkable silicone foam compositions, kits, and methods for filling implanted medical devices in situ or in vivo, the implanted medical devices, including for example, body implants and tissue expanders, the compositions including a platinum divinyl disiloxane complex; a low viscosity vinyl terminated polydimethylsiloxane; a low viscosity hydride terminated polydimethylsiloxane; a silicone cross-linker; and a gas and/or gas-filled microcapsules, where the rapidly cross-linkable silicone foam composition has a viscosity of ≤150 cPs for ≥1 min. post-preparation and ≤300 cPs≤5 min. post-preparation, at ambient temperature.

FIELD

The present disclosure relates generally to silicone compositions foruse in implanted devices.

BACKGROUND

Currently, implant devices, e.g., breast implants, are filled withconventional, thermally cured silicone gel, and then implanted into apatient. The volume of silicone contained in a silicone filled implanteddevice, cannot be adjusted post-implant. Further, already implanteddevices cannot be filled with a silicone gel after surgical implantationbecause current silicone gel formulations are highly viscous, forexample, having a viscosity of >1000 cPs; thus they are not injectablevia a hypodermic needle. In addition, currently used silicone gelformulations require thermal curing which cannot be carried out withregard to an already implanted device, or a device that is in theprocess of being surgically implanted or just before surgicalimplantation.

Current silicone foam compositions, where part of the volume of a foamfilled implant contains a gas such as air, also cannot be used to adjustthe volume of silicone post-implant or to initially fill an implantduring surgical implantation, because thermal curing required for thesecurrent formulations is not compatible with such foams, wherebyexpansion and contraction of the foam-forming gas during the thermalcuring cycle results in undesirable effects on the form and share ofgel.

SUMMARY

The presently described subject matter is directed to a two-part, RCSFcomposition, comprising or consisting of a catalyst fluid comprising afirst low viscosity vinyl terminated polydimethylsiloxane present in anamount of from about 97 wt % to about 99.5 wt % based on the weight ofthe catalyst fluid and having a viscosity of from about 1 to about 150cPs, and a platinum divinyl disiloxane complex comprisingPt[(CH₂═CH)(CH₃)₂SiOSi(CH₃)₂(CH═CH₂)]₃, having a platinum (Pt) contentof from about 2 to about 32 ppm based on the catalyst fluid, where thecatalyst fluid has a viscosity of from about 1 to about 150 cPs; and across-linker suspension comprising a second low viscosity vinylterminated polydimethylsiloxane present in an amount of from about 1 wt% to about 40 wt % based on the weight of the cross-linker fluid andhaving a viscosity of from about 1 to about 150 cPs, a low viscosityhydride terminated polydimethylsiloxane present in an amount of fromabout 60 wt % to about 90 wt % based on the weight of the cross-linkerfluid and having a viscosity of from about 1 to about 150 cPs, asilicone cross-linker comprising polymethylhydrosiloxanepolydimethylsiloxane copolymer present in an amount of from about 0.32wt % to about 5.0 wt % based on the weight of the cross-linker fluid,and having a viscosity of from about 1 to about 150 cPs, thecross-linker fluid has a viscosity of from about 1 to about 150 cPs, gasfilled microbubbles, such as foam-forming gas microbubbles, orgas-filled microcapsules, and optionally one or more surfactants.

The presently described subject matter is further directed to a kitcomprising a two-part, RCSF composition, according to the presentlydescribed subject matter, where the catalyst fluid is provided in afirst container, and the cross-linker suspension is provided in a secondcontainer.

The presently described subject matter is directed to a method offilling an implanted medical device in situ, comprising: providing a RCScomposition according to the presently described subject matter; mixingthe catalyst fluid with the cross-linker suspension to produce aninjectable composition having an initial viscosity of <150 cPs for atleast about 1 min.; and within ≤5 min. of initiating mixing, andsubstantially simultaneous with mixing, injecting a predetermined volumeof the injectable RCSF composition into the implanted medical device insitu, whereby the RCSF composition substantially cross-links and gels insitu in an amount of time ≥5 min. to produce a filled implant comprisingRCSF gel, where the RCSF gel can have a viscosity as described herein,post-injection at ambient temperature. The RCS gel can have a viscosity≥200,000 cPs≥60 min., ≥200,000 cPs≤24 hrs., ≥200,000 cPs≤12 hrs.,≥200,000 cPs≤6 hrs., ≥200,000 cPs≤3 hrs., ≥50,000 cPs≤24 hrs., ≥50,000cPs≥1 hr., ≥50,000 cPs≥1 hr. and ≤6 hrs., ≥50,000 cPs≥1 hr. and ≤12hrs., post-preparation or post-mixing at ambient temperature. Thepresently described subject matter is directed to any method accordingto the presently described subject matter, wherein the resultant RCSFfilled implant is free from any physical defect.

The presently described subject matter is directed to a method ofadjusting the volume of an implanted medical device in situ, comprising:providing a kit accordingly to the presently described subject matter;mixing the catalyst fluid with the cross-linker suspension to produce aninjectable composition having an initial viscosity of <150 cPs for atleast about 1 min.; and within ≤5 min of initiating mixing or within ≤10min. of initiating mixing, and/or substantially simultaneous withmixing, injecting a predetermined volume of the injectable compositioninto the implanted medical device in situ, whereby the RCSF compositionsubstantially cross-links and gels in situ in an amount of time ≥5 minor ≥5 min. to ≤10 min., or ≥10 min. to produce a filled implantcomprising RCSF gel, wherein the RCSF gel has a viscosity ≥50,000 cPs≥60min. post-injection at ambient temperature, and the volume of theimplanted device has been adjusted. The implanted medical device can bea permanent implant or a non-permanent implant according to thepresently described subject matter. The presently described RCSF gel canhave a viscosity ≥50,000 cPs≤24 post-injection at ambient temperature.

DETAILED DESCRIPTION Definitions

Any concentration ranges, percentage range, or ratio range recitedherein are to be understood to include concentrations, percentages orratios of any integer within that range and fractions thereof, such asone tenth and one hundredth of an integer, unless otherwise indicated.

About. As used herein, “about” refers to a degree of deviation based onexperimental error typical for the particular property identified. Thelatitude provided the term “about” will depend on the specific contextand particular property and can be readily discerned by those skilled inthe art. Further, unless otherwise stated, the term “about” shallexpressly include “exactly.”

Order of steps. It should also be understood that, unless clearlyindicated to the contrary, in any methods claimed herein that includemore than one step or act, the order of the steps or acts of the methodis not necessarily limited to the order in which the steps or acts ofthe method are recited.

Ambient Temperature. As used herein, the term “ambient temperature”refers to the temperature of the immediate environment. Ambienttemperature as used herein can refer to a temperature of from about 18°C. to about 40° C., including but limited to, from about 20° C. to about35° C., 20° C. to about 30° C., 20° C. to about 26° C., about 21° C.,about 22° C., about 23° C., about 24° C., or about 25° C.

Breast Implant. As used herein, the term “breast implant” refers to aprosthesis consisting of a gel-like or fluid material in a flexibleshell, implanted behind or in place of a breast in reconstructive orcosmetic surgery. The flexible shell can comprise a polymeric orelastomeric shell, including for example, a silicone shell, including asilicone elastomeric shell. The gel-like material or fluid material caninclude, for example, silicone gel or isotonic saline. The shell can bea single- or double-walled shell, or can include one or moredouble-walled areas. Suitable breast implants can be of any profile andsize, and can include MENTOR® breast implants including adjustableimplants including MENTOR® SPECTRUM® implants including SILTEX®implants, and BECKER design implants. Suitable implants come in a rangeof sizes, generally from 80 to 1000 cubic centimeters (cc) ormilliliters in volume, e.g., from about 80 to about 800 cc or mls.

Adjustable Breast Implant. As used herein, the phrase “adjustable breastimplant” refers to a breast implant that can be adjusted for volumeduring the implantation procedure or after healing of surgery. Aninitially empty inner shell or envelope can be later fully or partiallyfilled with gel to make the final size adjustment. Likewise, saline inan initially saline filled shell can be removed and replaced with thepresently described RCSF composition. The use of the presently describedRCSF composition as an adjustment medium provides a consistent feel withthe initial implanted gel implant, e.g., a cured silicone gel implant.Such implants can include, but are not limited to, a MENTOR® Beckerstyle implant having an outer shell having a volume that is filled toabout 75% to 95% with a cured gel (e.g., a conventional silicone gel),and, for example, an empty inner shell or envelope that can be filled atthe time of implantation or at a different time point after surgery,e.g., after healing or remission of swelling. Filling can beaccomplished via a valve to close the inner shell from the body. Morethan one fill port could be used and provide targeted fill adjustmentareas such as upper pole and lower pole fill zones. The inner envelopecan be attached to a bottom portion of the outer envelope and can definea volume of about 5% to about 15% or about 5% to about 10% of the volumeof the outer envelope and can be empty or filled with saline. Theimplant can also include a self-sealing valve and/or filling tube,and/or mini-reservoir for adjusting the size of the implant. Suitableadjustable implants include those described in U.S. Pat. No. 7,081,136hereby incorporated by reference in its entirety herein.

The terms “shell” and “envelope” are used interchangeably herein.Suitable implanted devices can include an elastomeric shell or envelope,including for example, but not limited to a silicone shell or envelope.A shell or envelope can comprise a double-walled shell or envelope,and/or a shell or envelope can comprise one or more double-walled areas.

Cure. As used herein, the term “cure” refers to a silicone polymer thathas ceased to flow and has a viscosity above the limit of a Brookfieldviscometer. The present RCSF compositions can cure ≤12 hrs, ≤24 hrs,from 6 hrs to 24 hrs, from 12 hrs to 24 hrs, or about 24 hours. Thepresent RCS compositions can be fully cured in about 24 hrs. Thepresently described RCS gels can have a viscosity of ≥200,000 cPs≥60min., ≥200,000 cPs≥6 hrs., ≥200,000 cPs≥12 hrs., ≥200,000 cPs≥24 hrs.,≥50,000 cPs≥60 min., ≥50,000 cPs≥6 hrs., ≥50,000 cPs≥12 hrs., or ≥50,000cPs≤24 hrs.

Flowable. As used herein, the term “flowable” refers to the ability of amaterial to run smoothly with unbroken continuity through a standardhypodermic needle, for example, through a standard gauge hypodermicsyringe. Suitable needles include but are not limited to 18 to 21 gaugeneedles.

Gas-Filled Microcapsules. As used herein, the term “gas-filledmicrocapsules” refers to microcapsules, including for example, polymericmicrocapsules, containing a gas, including for example, sterilized ornon-sterilized gases, including one or more of air, carbon dioxide,nitrogen, or oxygen, or any inert gas, where the gas-filledmicrocapsules are configured to be injected into an implanted medicaldevice via an 18 to 21 gauge needle. Suitable microcapsules and methodsof making the same, for use in the described RCSF compositions, includethose described in U.S. Pat. Nos. 6,622,633; 5,487,390; and 3,784,391,each of which is incorporated herein by reference in its entirety.Suitable microcapsules are available, for example, from COSPHERIC LLC,Santa Barbara, Calif., including clear polyethylene and glass, gasfilled microspheres. Suitable microcapsules can have an average diameterof <300μ, ≤100μ, ≤50μ, ≤30μ, ≤20μ, ≤15μ, ≤10μ, from about 1μ to about300μ, from about 1μ to about 100μ, from about 1μ to about 5μ, from about1μ to about 10μ, from about 1μ to about 20μ, from about 1μ to about 30μ,from about 1μ to about 40μ, from about 1μ to about 50μ, from about 10μto about 100μ, from about 10μ to about 50μ, from about 3μ to about 10μ,from about 3μ to about 20μ, from about 3μ to about 30μ, from about 3μ toabout 40μ, from about 3μ to about 50μ, or from about 3μ to about 5μ.

Implanted Medical Device. As used herein, the term “implanted medicaldevice” refers to any flexible medical device that is implanted in ananimal or for implantation in an animal, including but not limited to ahuman. Such devices can include permanent or non-permanent implantedmedical devices. Suitable permanent body implants can include but arenot limited to breast implants, adjustable breast implants, lumpectomyimplants, calf implants, tissue expanders, and any other body implantfor use in aesthetic and/or reconstructive surgery. Suitable permanenttissue expanders can include, for example, breast tissue expanders andcalf tissue expanders. Suitable non-permanent body implants can includenon-permanent tissue expanders including for example, non-permanentbreast tissue expanders and non-permanent calf tissue expanders.Implanted medical devices can comprise one or more of a fluid filledshell and an empty, unfilled shell. Suitable fluid filled shells caninclude a saline filled or a silicone, e.g., conventional thermallycured silicone gel, filled shell. Suitable implanted devices can includean elastomeric shell or envelope, including a silicone shell orenvelope. Suitable implanted medical devices can include one or morevalves or ports to allow for fluid addition or removal, for example,using a syringe. Such valves and/or ports can include self-sealingvalves or ports. The presently described implanted medical devices donot comprise solid implants, for example, solid silicone implants.

Suitable implanted medical devices can be permanent silicone shellimplants where the volume can be adjusted by injection of the inventivefoam composition.

In Situ. As used herein, the term “in situ” refers to cross-linking ofthe RCSF composition substantially within an implant that had previouslybeen implanted in a subjects body That is, the RCSF compositionsubstantially cross-links in its desired and optimal position, i.e.,within the already implanted medical device.

Injection. As used herein, the term “injection” refers to theadministration of the presently described RCSF composition into animplant device. Injection may or may not be through a valve, and may ormay not be via a port. Injection can be performed directly through awall of an implant device comprising, for example, a polymeric orelastomeric wall, such as a silicone or a silicone elastomer wall. Wheninjection is directly through the shell of an implanted device (i.e.,not via a valve or port), rapid cross-linking of the silicone gelresults in the rapid formation of a gel plug in the shell of theimplanted device, at the site of injection (i.e., needle stick site),thereby preventing any potential leakage of the gel from the implant atthe site of injection. Further, when adding a RCSF composition to animplanted medical device containing thermally cured silicone, the RCSFcomposition can be injected at a location behind a portion of existinggel inside the implanted device.

Injection Device. As used herein, the term “injection device” refers toa device configured to administer by injection, an RCSF compositioncomprising two reactive components that cannot be supplied or stored asa single mixture. Such devices can include dual prefilled syringes eachcontaining a respective component, connected via, e.g., a Y-connectoroptionally comprising a mixer, e.g., a static mixer; and dual cartridgedispensing systems, including for example, those produced by PLAS-PAKIndustries, Inc., Norwich, Conn., which can be used with static mixersand include syringes having variable volumes up to 750 ml per cartridge,and include cartridge combinations that produce various mix ratios.Other suitable devices can include, but are not limited to, dual boredevices, and dual chamber syringes. Dual chamber syringes can include,for example, those manufactured by CREDENCE MedSystems, Inc., MenloPark, Calif., which include Companion Dual Chamber Syringeliquid-liquid.

According to the presently described subject matter, an injection devicecan comprise a syringe with attached hypodermic needle, where thesyringe is filled with the already mixed RCS composition.

Lumpectomy Implant. As used herein, the term “lumpectomy implant” refersto a football shaped shell configured to fit into lumpectomy excisionduring implantation into a lumpectomy void, where the shell can beimplanted unfilled and filled in situ with the presently described RCSFcomposition, at the time of lumpectomy or as a later revision surgery.After injecting the RCSF composition into the lumpectomy shell,compression can be applied to ensure that the silicone gel conforms tothe natural surrounding tissue such that upon cross-linking and curing,the silicone gel filled implant blends with the natural breast tissue,whereby no defects are visible.

Physical Defect. As used herein, the term “physical defect” refers toany flaw or imperfection present in an implanted medical device. Suchphysical defects can include gel fracture (e.g., cracks in the gel), oneor more lumps, wrinkling, and/or demarcation. The presently describedRCSF compositions can be used to ameliorate or eliminate any suchphysical defect present in an existing implanted medical device. Afterinjection and gelling and/or cure of the present RCSF composition, abody implant is free from any physical defects, and/or any existingphysical defect is ameliorated or eliminated. The implanted medicaldevice can be a silicone gel containing implant.

Pot Life. As used herein, the term “pot life” refers to the period oftime that the presently described RCSF after mixing, remains low enoughin viscosity that it can still be sufficiently flowable such that it canbe injected into an implanted device, e.g., via an 18 to 21 gaugeneedle. The terms “pot life” and “working life” as used interchangeablyherein.

Silicone Gel. As used herein, the term “silicone gel” refers to anycross-linked, gelled, or cured, silicone gel formulation or composition.

Mixer. As used herein, the term “mixer” refers to a mechanical mixerconfigured to mix two components of the presently describedtwo-component system and kit, prior to injection. Such mixers caninclude static mixers, including known static mixers, e.g., produced byPVA, Cohoes, N.Y.

Two components, namely the catalyst fluid and the cross-linker fluid,can also be mixed by combining these fluids in a container, and thenmixing by any known means, such as by mechanical stirring or shaking,until substantially mixed, prior to injecting. Alternatively twocomponents namely the catalyst fluid and the cross-linker fluid can bemixed by placing these fluids into two separate syringes and connectingthese syringes by a connector and then transferring the fluids from onesyringe to another back and forth several times, until substantiallymixed, prior to injecting.

Subject. As used herein, the term “subject” refers to any animalincluding for example, a human, having a flexible implanted medicaldevice.

Tissue Expander. As used herein, the term “tissue expander” refers to aninflatable implant designed to stretch the skin and muscle. Tissueexpanders can be permanent or non-permanent tissue expanders. Suitablebreast tissue expanders can include but are not limited to breast tissueexpanders including MENTOR® tissue expanders, e.g., CPX®3, CPX®4,ARTOURA™; and ALLERGAN Tissue Expanders. Tissue expanders can alsoinclude other tissue expanders, for example, calf tissue expanders.

Rapidly Cross-Linkable Silicone Foam Compositions and Methods

The presently described subject matter is directed to novel, injectable,RCSF compositions for filling an implanted medical device in situ.

The RCSF compositions can be injected as a pre-mixed formulationincluding a sterile gas or gas-filled microcapsules. The compositionscan be injected as a two-part formulation, including a catalyst fluidand a cross-linker suspension containing a sterile gas or gas-filledmicrocapsules, that can be injected via, for example, a injection deviceconfigured to separate the two components, where the components mix uponadministration, e.g., injection into an implanted medical device. Thecompositions can be injected as a two-part formulation, including afirst pre-mixed RCS formulation and a sterile gas, that can be injectedvia, for example, a injection device configured to separate the twocomponents, where the components mix upon administration, e.g.,injection into an implanted medical device. Alternatively, the RCSFcompositions can be injected as a three-part formulation including acatalyst fluid, a cross-linker fluid, and a sterile gas, that can beinjected via, for example, a injection device configured to separate thethree components, where the components mix upon administration, e.g.,injection into an implanted medical device via a static mixer or it canbe pre-mixed prior to injection.

The presently described RCSF formulations are injectable via ahypodermic syringe comprising e.g., an 18 to 21 gauge needle.

The amount of sterile gas or gas-filled microcapsules can be selectedbased on a pre-determined desired bulk density of the resultant RCSFgel. For example, the amount of gas or gas-filled microcapsules employedin the present RCSF formulations is inversely proportional to the bulkdensity of the resultant RCSF gel.

The presently described RCSF formulations contain no solvent orsubstantially no solvent that would need to be removed during or aftercuring. Such formulations can include, for example, the describedtwo-part formulations (e.g., where mixing and injecting are performedsubstantially simultaneously through an injection device that separatesthe components up to point of use), three-part formulations (e.g., wheremixing and injecting are performed substantially simultaneously throughan injection device that separates the components up to point of use),as well as the pre-mixed formulations (where the components are firstmixed and then injected, e.g., through a single syringe), contain nosolvent or substantially no solvent that would need to be removed duringor after curing.

Upon mixing, either prior to injection (pre-mixed formulation) orsubstantially simultaneous with injection (two-component formulation orthree-component formulation), the components of the presently describedRCSF formulations react and within minutes form a gel inside theimplanted medical device. Upon mixing or mixing and substantiallysimultaneous injection, the RCSF composition has a pot life of about≤five min., where the mixture maintains low viscosity and highflowability, such that it can be injected using a hypodermic needle,e.g., an 18 to 21 gauge hypodermic needle, where the RCSF compositionsubstantially gels, and cures, in situ in the implanted medical device.

The presently described injectable, two-part RCSF formulations cancomprise or consist of two highly flowable low viscosity fluids, whichrapidly cross-link upon mixing and injection, such that the RCSFcomposition gels and fully cures in-situ, at ambient or body temperatureinside an implanted medical device. When, prior to injection, theimplanted medical device comprises a conventional silicone gel, thepresently described RCSF gel can have substantially the same propertiesas that of the conventional silicone gel.

Each component of a RCSF two-component formulation can be provided in arespective first and second syringe of an injection device, the syringesconnected via a Y-connector connected to a mixer, e.g., a static mixer.Alternatively, the present RCSF compositions can also be pre-mixed andthen injected via a single syringe.

In some embodiments, the size of an implanted medical device containingconventional thermally cured silicone gel, can be increased, as needed,by infusing, e.g., by injecting, the presently described RCSFcomposition into the implanted medical device, where the presentcomposition then rapidly gels and cures in situ. The gel contained inthe resulting enlarged implant including the RCSF gel and theconventional silicone gel, can be consistent throughout with regard toits physical properties and can be free from physical defect, e.g., nolumps or gel fracture observed in the implanted medical device.

In other aspects, saline contained in implanted non-permanent tissueexpanders can be replaced with the present RCSF composition. In otheraspects, the saline in saline filled breast implants can be replacedwith the presently described RCSF compositions.

The RCSF composition can have a viscosity at ≤5 min post-preparation orpost-mixing that is sufficiently low so that the composition is flowableand can be injected via an 18 to 21 gauge needle. Suitable viscositiescan include ≤300 cPs, ≤250 cPs, ≤200 cPs, ≤150 cPs, ≤100 cPs, from about80 cPs to about 300 cPs, from about 100 cPs to about 300 cPs, from about100 cPs to about 250 cPs, from about 200 cPs to about 300 cPs, fromabout 100 cPs to about 250 cPs, from about ≥80 cPs to about ≤300 cPs,from about ≥100 cPs to about ≤300 cPs, from about ≥125 cPs to about ≤300cPs, or from about ≥150 cPs to about ≤275 cPs. The viscosity ≤5 min.post-mixing can be ≤250 cPs.

The presently described RCSF composition according to the presentlydescribed subject matter can gel, post-mixing, in an amount of time fromabout ≥5 min., >5 min., or from about 5 min. to about 15 min. Thepresently described RCSF compositions can gel in about ≥5 min., or fromabout 6 to about 10 min., and can form a fully cured gel within about 12hours or within about 24 hours.

The presently described RCSF composition according to the presentlydescribed subject matter can cure in ≤12 hrs., ≤24 hrs., from about 6hrs. to about 24 hrs. from about 6 hrs. to about 12 hrs., about 8 hrs.,about 10 hrs., about 12 hrs., about 14 hrs., about 18 hrs., about 22hrs., or about 24 hrs.

The viscosity of the presently described RCSF compositions increasespost-injection such that the gel cannot flow; thus any leakage of thegel from the implant through the injection hole is not possible. Theformed gel plugs any channels left by an infusion needle in the implant.The RCSF compositions can be injected through a wall of an implantshell, and do not have to be injected via a valve or a port. Further,injection can be through a double-walled or double-walled area of ashell of an implant. A double-walled shell or shell area also can serveto prevent any potential leakage. When injection of the present RCSFcomposition is into an implanted device containing conventionalsilicone, the RCSF composition can be injected behind a portion of theconventional silicone, which can prevent any potential leakage.

The presently described RCSF composition, injectable, for example, as atwo-part formulation, can include a first container comprising acatalyst fluid comprising a platinum divinyl disiloxane complex and alow viscosity vinyl terminated polydimethylsiloxane; and a secondcontainer comprising a cross-linker suspension comprising a lowviscosity vinyl terminated polydialkylsiloxane, a low viscosity hydrideterminated polydimethylsiloxane, a silicone cross-linker, and gas-filledmicrocapsules according to the presently described subject matter.Suitable cross-linkers include but are not limited topolymethylhydrosiloxane polydimethylsiloxane copolymer.

The presently described an injectable, RCSF composition, can comprise orconsist of a catalyst fluid comprising a first low viscosity vinylterminated polydimethylsiloxane present in an amount of from about 97 wt% to about 99.5 wt % based on the weight of the catalyst fluid andhaving a viscosity of from about 1 to about 150 cPs, and a platinumdivinyl disiloxane complex having from about 2 to about 32 ppm Pt basedon the catalyst fluid, wherein the catalyst fluid has a viscosity offrom about 1 to about 150 cPs; and a cross-linker suspension comprisinga second low viscosity vinyl terminated polydimethylsiloxane present inan amount of from about 1 wt % to about 40 wt % based on the weight ofthe cross-linker fluid and having a viscosity of from about 1 to about150 cPs, a low viscosity hydride terminated polydimethylsiloxane presentin an amount of from about 60 wt % to about 90 wt % based on the weightof the cross-linker fluid and having a viscosity of from about 1 toabout 150 cPs, a siloxane cross-linker present in an amount of fromabout 0.32 wt % to about 5.0 wt % based on the weight of thecross-linker fluid, and having a viscosity of from about 1 to about 150cPs, and gas-filled microcapsules. The cross-linker suspension can havea viscosity of from about 1 to about 150 cPs, and whereinpost-preparation, the resultant RCSF composition has a viscosity of ≤150cPs for at least one minute and a pot-life of ≤5 min., at ambienttemperature. The resultant RCSF composition can have a Pt content offrom about 1 ppm to about 16 ppm. The catalyst fluid can be provided ina first container and the cross-linker suspension can be provided in asecond container.

Such implanted medical devices can include, but are not limited to:breast implants including for example, any known breast implant, anadjustable implant, for example, a multi-lumen breast implant, where theimplant can comprise an inner and an outer envelope, the breast implantcan comprise one or more valves and/or ports, optionally includingflexible tubing; lumpectomy implants; calf implants; tissue expanders,including but not limited to, breast tissue expanders, and calf tissueexpanders; and any other gel or fluid filled body implant useful forcosmetic and/or reconstructive purposes. Suitable tissue expanders caninclude permanent tissue expanders.

Implanted medical devices can include, but are not limited to thosemedical implant devices according to the presently described subjectmatter. An implant shell can comprise a single-walled shell or adouble-walled shell and/or one or more areas that are one or more of asingle-walled area and a double-walled area.

The present low viscosity vinyl terminated siloxane polymers can includevinyl terminated polydialkylsiloxane, including vinyl terminatedpolydimethylsiloxane, including DMS-V21 and DMS-V22 available fromGELEST, Morrisville, Pa. Vinyl terminated polydimethylsiloxane, DMS-V21can be used in the presently described RCS compositions.

Suitable low viscosity hydride terminated polydimethylsiloxanes caninclude, but are not limited to, DMS-H21 available from GELEST,Morrisville, Pa.

Suitable siloxane cross-linkers for use in the presently describedcompositions can include methylhydride siloxane dimethyl siloxanecopolymer, available from GELSET HMS-301, and HMS-501, Morrisville, Pa.

Other cross-linkers can include, for example, silicone cross-linkingagents including, for example, polymethylhydro siloxane,polymethylhydro-co-polydimethylsiloxane, polyethyhydrosiloxane,polymethylhydrosiloxane-co-octylmethylsiloxane, andpolymethylhydrosiloxane-co-methylphenylsiloxane.

Suitable platinum divinyl disiloxane complex catalyst, can includeKarstedt catalyst, e.g., Pt[(CH₂═CH)(CH₃)₂SiOSi(CH₃)₂(CH═CH₂)]₃,including GELEST SIP 6831.2 available from GELEST, Morrisville, Pa.Suitable catalysts are described in U.S. Pat. No. 3,775,452,incorporated herein by reference in its entirety.

The presently described catalyst fluid component can comprise platinumdivinyl disiloxane having a platinum content of from about 2 ppm toabout 32 ppm, from about 4 ppm to about 28 ppm, from about 4 ppm toabout 20 ppm, from about 6 ppm to about 14 ppm, from about 6 ppm toabout 12 ppm, from about 4 ppm to about 12 ppm, from about 4 ppm toabout 6 ppm, from about 4 ppm to about 8 ppm, about 4 ppm, about 6 ppm,about 8 ppm, about 10 ppm, about 12 ppm, about 14 ppm, about 20 ppm,about 26 ppm, or about 32 ppm.

The platinum content of the presently described RCSF composition can befrom about 1 ppm to about 16 ppm, from about 1 ppm to about 10 ppm, fromabout 1 ppm to about 8 ppm, from about 2 ppm to about 10 ppm, from about2 ppm to about 8 ppm, from about 1 ppm to about 6 ppm, from about 1 ppmto about 4 ppm, about 2 ppm, about 3 ppm, about 4 ppm, about 5 ppm,about 6 ppm, about 7 ppm, or about 8 ppm.

The presently described platinum divinyl disiloxane can have a viscosityof from about 1 to about 150 cPs or from about 80 to 120 cPs. Thepresently described catalyst fluid can have a viscosity of from about 1to about 150 cPs or from about 80 to 120 cPs.

The presently described first low viscosity vinyl terminatedpolydimethylsiloxane can be present in the catalyst fluid in an amountof from about 96 wt % to about 99.5 wt %, of from about 96.5 wt % toabout 99.5 wt %, of from about 97 wt % to about 99.5 wt %, of from about97.25 wt % to about 99.25 wt %, of from about 97.5 wt % to about 99 wt%, of from about 97.75 wt % to about 98.75 wt %, of from about 98 wt %to about 98.5 wt %, of from about 98 wt % to about 98.25 wt %, of fromabout 97.5 wt % to about 98.5 wt %, of from about 97.75 wt % to about98.75 wt %, about 97 wt %, about 97.5 wt %, about 98 wt %, about 98.4 wt%, about 98. 5 wt %, about 99 wt %, or about 99.5 wt %.

The presently described first low viscosity vinyl terminatedpolydimethylsiloxane and the second low viscosity vinyl terminatedpolydimethylsiloxane, together, can be present in the RCSF compositionin an amount of from about 45 wt % to about 95 wt %, from about 50 wt %to about 90 wt %, from about 55 wt % to about 85 wt %, from about 60 wt% to about 80 wt %, from about 65 wt % to about 75 wt %, about 60 wt %,about 65 wt %, about 70 wt %, about 75 wt %, about 80 wt %, about 85 wt%, or about 90 wt %.

The presently described first low viscosity vinyl terminatedpolydimethylsiloxane can have a viscosity of from about 1 to about 150cPs or from about 80 to 120 cPs.

The presently described second low viscosity vinyl terminatedpolydimethylsiloxane can be present in the cross-linker fluid in anamount of from about 1 wt % to about 40 wt %, of from about 5 wt % toabout 40 wt %, of from about 5 wt % to about 35 wt %, of from about 7 wt% to about 32 wt %, of from about 8 wt % to about 31 wt %, of from about10 wt % to about 30 wt %, of from about 12 wt % to about 38 wt %, offrom about 14 wt % to about 26 wt %, of from about 15 wt % to about 25wt %, of from about 18 wt % to about 23 wt %, from about 19 wt % toabout 22 wt %, from about 17 wt % to about 22 wt %, from about 18 wt %to about 21 wt %, from about 19 wt % to about 20 wt %, about 15 wt %,about 16 wt %, about 17 wt %, about 18 wt %, about 19 wt %, about 19.5wt %, about 20 wt %, about 21 wt %, or about 22 wt %.

The presently described second low viscosity vinyl terminatedpolydimethylsiloxane can have a viscosity of from about 1 to about 150cPs or from about 80 to 120 cPs. The presently described cross-linkerfluid can have a viscosity of from about 1 to about 150 cPs or fromabout 80 to 120 cPs.

The presently described low viscosity hydride terminatedpolydimethylsiloxane is present in the cross-linker composition in anamount of from about 55 wt % to about 95 wt %, of from about 60 wt % toabout 90 wt %, of from about 65 wt % to about 85 wt %, of from about 70wt % to about 85 wt %, of from about 75 wt % to about 85 wt %, of fromabout 76 wt % to about 84 wt %, of from about 77 wt % to about 83 wt %,of from about 78 wt % to about 82 wt %, of from about 79 wt % to about81 wt %, about 77 wt %, about 78 wt %, about 79 wt %, about 80 wt %,about 80.5 wt %, about 81 wt %, about 82 wt %, about 83 wt %, or about84 wt %.

The presently described low viscosity hydride terminatedpolydimethylsiloxane can be present in the RCS composition in an amountof from about 25 wt % to about 55 wt %, from about 30 wt % to about 50wt %, from about 35 wt % to about 45 wt %, about 30 wt %, about 35 wt %,about 40 wt %, about 45 wt %, or about 50 wt %.

The presently described low viscosity hydride terminatedpolydimethylsiloxane can have a viscosity of from about 1 to about 150cPs or from about 80 to 120 cPs.

The presently described siloxane cross-linker is present in thecross-linker fluid component in an amount of from about 0.1 wt % toabout 7 wt %, from about 0.15 wt % to about 6 wt %, from about 0.2 wt %to about 6 wt %, from about 0.3 wt % to about 6 wt %, from about 0.32 wt% to about 5 wt %, from about 0.4 wt % to about 4 wt %, from about 0.4wt % to about 3 wt %, from about 0.3 wt % to about 2 wt %, from about0.3 wt % to about 3 wt %, from about 0.3 wt % to about 1 wt %, fromabout 0.4 wt % to about 3 wt %, from about 0.4 wt % to about 2 wt %,from about 0.6 wt % to about 3 wt %, from about 0.7 wt % to about 2 wt%, from about 0.8 wt % to about 2 wt %, from about 1 wt % to about 2 wt%, from about 1.2 wt % to about 1.8 wt %, from about 0.2 wt %, about 0.3wt %, about 0.32 wt %, about 0.4 wt %, about 0.5 wt %, about 0.6 wt %,about 1 wt %, about 1.4 wt %, about 1.6 wt %, about 1.8 wt %, about 2 wt%, about 2.5 wt %, about 3 wt %, about 3.5 wt %, about 4 wt %, about 4.5wt %, or about 5 wt %.

The presently described siloxane cross-linker can be present in the RCScomposition in an amount of from about 0.05 wt % to about 3.5 wt % offrom about 0.1 wt % to about 3 wt %, of from about 0.16 wt % to about2.5 wt %, of from about 0.2 wt % to about 2.5 wt %, of from about 0.2 wt% to about 2 wt %, of from about 0.25 wt % to about 2 wt %, of fromabout 0.3 wt % to about 2 wt %, of from about 0.13 wt % to about 2.2 wt%, of from about 0.14 wt % to about 2.1 wt %, of from about 0.15 wt % toabout 2.1 wt %, of from about 0.16 wt % to about 2 wt %, from about 0.18wt % to about 1.8 wt %, from about 0.2 wt % to about 1.6 wt %, fromabout 0.4 wt % to about 1.4 wt %, from about 0.6 wt % to about 1.2 wt %,from about 0.8 wt % to about 1 wt %, about 0.15 wt %, about 0.2 wt %,about 0.3 wt %, about 0.4 wt %, about 0.5 wt %, about 0.6 wt %, about0.8 wt %, about 1 wt %, about 1.2 wt %, about 1.4 wt %, about 1.6 wt %,about 1.8 wt %, about 2 wt % or about 2.5 wt %.

The presently described siloxane cross-linker can have a viscosity offrom about 1 to about 150 cPs or from about 25 to 35 cPs.

The presently described two-part formulation of the present RCSFcomposition is flowable and has a viscosity <150 cPs for at least 1minute after forming or mixing at ambient temperature. The compositionhas a viscosity >300 cPs at about 10 minutes after forming or mixing atambient temperature. The gelled composition can have a viscosity ≥50,000cPs≤24 after forming or mixing and/or injecting at ambient temperature.

The presently described RCSF pre-mixed formulation, injectable, forexample, after mixing via a single syringe, can include a platinumdivinyl disiloxane complex having a Pt content of from about 1 ppm toabout 16 ppm as described herein, a low viscosity vinyl terminatedpolydimethylsiloxane present in an amount of from about 55.0 wt % toabout 80.0 wt %, a low viscosity hydride terminated polydimethylsiloxanepresent in an amount of from about 35.0 wt % to about 45.0 wt %, across-linker present in an amount of from about 0.16 wt % to about 2.5wt %, and gas-filled microcapsules as described herein. The presentlydescribed RCSF composition can include the low viscosity vinylterminated polydimethylsiloxanes present in an amount of about 60 wt %,the low viscosity hydride terminated polydimethylsiloxanes present in anamount of about 40 wt %, and the siloxane cross-linker is present in anamount of about 0.16 wt %.

The presently described two-part formulations of the presently describedRCSF compositions can be prepared for injection into an implantedmedical device, the method can comprise a method for adjusting thevolume of an implanted medical device; ameliorating or eliminating aphysical defect in a filled implanted medical device, including forexample, lumps, wrinkles, gel fractures, demarcation, or any otherphysical defect; filling or gradually filling an implanted, unfilledtissue expander; replacing saline in an implanted medical devicecomprising saline; filling an unfilled envelope or shell of an implanteddevice, including for example an adjustable breast implant; or employingthe present composition in a permanent tissue expander in place ofsaline.

The methods as described herein, including for example, filling,adjusting, replacing, expanding, and ameliorating, can comprise thefollowing steps: providing a RCSF composition or kit according to thepresently described subject matter; mixing the catalyst fluid with thecross-linker suspension to produce an injectable composition having aninitial viscosity of <150 cPs for at least about 1 min; and within ≤5min. of initiating mixing, and substantially simultaneous with mixing,or immediately after mixing, for example, within 5 min. of mixing, orwithin 10 min. of mixing, injecting a predetermined volume of theinjectable composition into the implanted medical device in situ,whereby the RCSF composition substantially cross-links and gels in situin an amount of time ≥5 min. to produce a filled implant comprising RCSFgel, wherein the rapidly cross-linkable silicone gel has a viscosity asdescribed herein, for example, ≥50,000 cPs, or ≥200,000 cPs≥60 min.post-injection at ambient temperature. The presently described RCSF gelcan have a ≥50,000 cPs≤24 post-injection at ambient temperature.

RCSF formulations can be prepared by introducing a sterile gas, e.g.,air, into a liquid RCS composition. The RCS composition can be preparedaccording to the presently described subject matter Immediately aftermixing the catalyst fluid and the cross-linker fluid, sterile gas can bebubbled, via a narrow cannnula (or a tube) into the mixed liquid RCScomposition, thereby forming a foam.

To prevent gas from escaping from the RCS liquid composition during orafter bubbling a gas into the composition, one or more of the followingcan be performed: bubbling can commence during or immediatelypost-mixing and can be carried out at least until the RCS bubbled liquidbegins to gel, e.g., at least until a viscosity of ≥150 cPs and ≤500 cPsis reached (as described herein), and optionally for a time sufficientto produce a desired volume of microbubbles; or bubbling can commenceafter the RCS mixed liquid begins to gel, e.g., after a viscosity of≥150 cPs and ≤500 cPs is reached, and optionally can be carried out fora time sufficient to produce a desired volume of microbubbles.

When gas is bubbled into an RCS composition as the RCS compositionbegins to cross-link and gel, e.g., at or after about 1 min., about 1.5min., about 2 min., about 2.5 min., about 3 min., about 3.5 min., about4 min., or about 5 min post-mixing, and while the RCS composition isstill injectable through, for example, an 18-21 gauge needle, the gasbubbles became entrapped in the silicone matrix, and the rapidlycross-linkable silicone foam forms. Once the foam is formed or begins toform, it can then be immediately injected, for example, via an injectiondevice.

The bulk density of the formed cured RCSF can be about 50% of the bulkdensity of the RCS composition itself. The bulk density of the RCSF canbe about 20% to about 90% of that of a corresponding RCS composition,about 25% to about 85%, about 25% to about 80%, about 30% to about 75%,about 35% to about 70%, about 40% to about 65%, about 45% to about 60%,about 45% to about 55%, or about 50% of that of a corresponding RCScomposition.

The step of bubbling a gas, e.g., sterile air, into a mixed RCScomposition, can be carried at least until the RCS mixed liquid to beginto gel or to gel, for example, bubbling can be carried out for a periodof time sufficient for the bubbled composition to reach a viscosity of,for example, ≥150 cPs to ≤500 cPs, ≥150 cPs to ≤400 cPs, ≥200 cPs to≤500 cPs, ≥150 cPs to ≤300 cPs, ≥200 cPs to ≤350 cPs, ≥150 cPs to ≤250cPs, ≥150 cPs to ≤350 cPs, ≥200 cPs to ≤300 cPs, ≥200 cPs to ≤400 cPs,≥250 cPs to ≤500 cPs, ≥250 cPs to ≤450 cPs, ≥250 cPs to ≤400 cPs, ≥250cPs to ≤350 cPs, ≥300 cPs to ≤500 cPs, ≥300 cPs to ≤450 cPs, ≥300 cPs to≤400 cPs, ≥300 cPs to ≤350 cPs, ≥350 cPs to ≤500 cPs, ≥350 cPs to ≤450cPs, ≥350 cPs to ≤400 cPs, ≥400 cPs to ≤500 cPs, or ≥400 cPs to ≤450cPs. A suitable amount of time can include ≥1 min. to about ≤5 min.

Bubbling can be carried out for a period of time, simultaneously withmixing, substantially simultaneously with mixing, immediatelypost-mixing, or ≥1 min. to about ≤5 min. post-mixing, sufficient toproduce a foam wherein microbubbles comprise, e.g., from about 10%vol/vol to about 55% vol/vol of the RCSF composition, as describedherein.

Bubbling can commence, once the RCS mixed liquid begins to gel or gels,for example, bubbling can commence in from about ≥1 min. to about ≤5min. post-preparation or post-mixing.

The RCS composition begins to cross-link and gel, for example afterabout 1 to about 4 minutes post-preparation or post mixing, for examplewhen the RCS gel had reached a viscosity of ≥150 cPs to ≤500 cPs, ≥150cPs to ≤400 cPs, ≥200 cPs to ≤500 cPs, ≥150 cPs to ≤300 cPs, ≥200 cPs to≤350 cPs, ≥150 cPs to ≤250 cPs, ≥150 cPs to ≤350 cPs, ≥200 cPs to ≤300cPs, ≥200 cPs to ≤400 cPs, ≥250 cPs to ≤500 cPs, ≥250 cPs to ≤450 cPs,≥250 cPs to ≤400 cPs, ≥250 cPs to ≤350 cPs, ≥300 cPs to ≤500 cPs, ≥300cPs to ≤450 cPs, ≥300 cPs to ≤400 cPs, ≥300 cPs to ≤350 cPs, ≥350 cPs to≤500 cPs, ≥350 cPs to ≤450 cPs, ≥350 cPs to ≤400 cPs, ≥400 cPs to ≤500cPs, or ≥400 cPs to ≤450 cPs.

The injected RCSF gel remains in the implant post-injection withoutleakage of the gel from the injection site.

The presently described RCSF filled implant can be free from anyphysical defect. When the present method is directed to eliminating orameliorating a physical defect present in an implanted medical device,the physical defect is ameliorated or eliminated post-injection (orpost-injection and post-gelling and/or post-cure) of the present RCSFcomposition.

Any one or more of the methods as described herein, can comprise:mixing, for example, rapidly mixing, for example at an ambienttemperature, a catalyst fluid and a cross-linker suspension of thepresently described two-component formulation of the present RCSFcomposition, the produced RCSF composition having an initial viscosityof <150 cPs; within about 5 minutes post-mixing, injecting produced RCSFcomposition into the implanted medical device, for example, an implantedmedical device as described herein, through a hypodermic needle of aninjection device, e.g., using for example, one or more syringes,according to the presently described subject matter; allowing theinjected RCSF composition to cross-link, for example, for a period oftime sufficient for the injected composition to gel, inside the implantat an ambient temperature; and withdrawing the hypodermic needle fromthe implant, whereby the injected RCSF gel remains in the implantpost-injection without leakage of the gel from the injection site. Theinjection device can comprise an injection device as presently describedherein including a hypodermic needle that is an 18 to 21 gauge needle.

Any one or more steps of the presently described method may or may notbe carried out at ambient temperature. Ambient temperature is from about18° C. to about 40° C., as described herein.

According to the presently described subject matter, at least the stepsof injecting and allowing are carried out at ambient temperature,including, e.g., room temperature. The step of allowing can be carriedout at normal body temperature.

The steps of mixing and injecting can be carried out simultaneously,substantially simultaneously, or sequentially.

The step of withdrawing can comprise withdrawing the needle immediatelypost-injection, from about 0.02 to 5 min. post-injection, from about0.05 to about 1 min., from about 0.05 to about 2 min., from about 0.05to about 3 min., from about 0.1 to about 3 min. from about 0.2 to about3 min., from about 0.2 to about 2 min., from about 0.2 to about 1 min.,from about 0.2 to about 0.5 min., from about 0.3 to about 3 min., fromabout 0.3 to about 1 min., about 0.05 min., about 0.1 min., about 0.2min., about 0.3 min., about 0.4 min., about 0.5 min., or about 1 min.

An injection scheme can include injecting the presently describedpre-mixed RCSF formulation of the present RCSF composition containing asterile gas or gas-filled microcapsules, through a single syringeincluding injection needle, e.g., an 18-21 gauge needle, into animplanted medical device, according to the presently described subjectmatter.

Another injection scheme can include injecting the presently describedtwo-part RCSF formulation, including a catalyst fluid and a cross-linkersuspension comprising a sterile gas or gas-filled microparticles, intoan implanted medical device, e.g., a silicone breast implant, through aninjection device including two syringes and a mixing tip, where onesyringe comprises the catalyst fluid and the other syringe comprises thecross-linker suspension. Upon actuating the pair of plungers of thesyringes of the injection device during injection, the two componentsintimately mix in the mixing tip, to form a homogeneous foamed masswhich rapidly cross-links post-mixing, where the two-part formulation issimultaneously or substantially simultaneously mixed in the mixing tipand injected into the implanted device, e.g., an implanted breastimplant.

A further injection scheme can include preparing an RCS composition thatdoes not contain a sterile gas and does not contain gas-filledmicrocapsules, contained in a first syringe of a dual syringe injectiondevice comprising a mixing tip as described herein, and providing asterilized gas in a second syringe of the dual syringe injection device.Upon actuating the pair of plungers of the syringes of the injectiondevice during injection, the two components intimately mix in the mixingtip, to form a homogeneous foamed mass which rapidly cross-linkspost-mixing, where the two-part formulation is simultaneously orsubstantially simultaneously mixed in the mixing tip and injected intothe implanted device as described herein.

Yet another injection scheme can include injecting a three-part RCSFformulation including a two-part RCS formulation containing a catalystfluid and a cross-linker fluid, that does not contain a sterile gas anddoes not contain gas-filled microcapsules, and a sterile gas, where thethree components are contained separately and are not in physical orreactive contact until point of use. For example, the injection devicecan comprise a dual chamber syringe and a single chamber syringeconnected via a connector and a mixing tip, e.g., a static mixer, wherethe catalyst fluid and the cross-linker fluid are contained in arespective chamber of the dual chamber syringe, and the sterile gas iscontained in the single chamber syringe. For example, the two componentsof the RCS composition can be mixed in the dual chamber device, and theresultant RCS composition can intimately mix in the mixing tip with thesterile gas upon injection, to form a homogeneous foamed mass whichrapidly cross-links, where mixing and injecting are simultaneously orsubstantially simultaneously carried out.

In another aspect, all three components can be mixed forming a foamwhich is then transferred into a single syringe for injection. Mixingcan be done by mechanical agitation, by bubbling as into the liquid RCS,or by moving back and forth the components from one syringe to anothersyringe connected by a luer lock connector until a homogenous foam isformed.

EXAMPLES Example 1: Preparation and of Pre-Mixed Formulation of aRapidly Cross-Linkable Silicone (RCS) Composition with Variable PlatinumContent

In this Example, the RCS compositions were pre-mixed prior to injection,i.e., were injected as a single composition. The resulting mixturesremained injectable with low viscosity up to 5 minutes post-mixing, andwere easily flowable through a hypodermic needle after mixing. Theprocess window (pot-life) was about 5 minutes prior to injection. Thepreparation of the composition was as follows:

Step 1. Catalyst Fluid Preparation:

1 g of Karstedt catalyst Platinum divinyl disiloxane complex, containing2% Pt[(CH₂═CH)(CH₃)₂SiOSi(CH₃)₂(CH═CH₂)]₃ in xylene (obtained fromGELSET SIP 6831.2) was mixed with 99 g of low viscosity (100 cPs) vinylterminated polydimethylsiloxane (GELSET DMS V21) for 5 minutes atambient temperature to obtain a homogeneous solution.

Step 2. Cross-Linker Fluid Preparation:

For each of the test compositions 1-4 set forth in Table 1 below, 60 gof low viscosity vinyl terminated polydimethylsiloxane (Gelest DMS V21)was mixed with 40 g of low viscosity hydride terminatedpolydimethylsiloxane (GELEST DMS H21), and 0.16 g cross linker(methylhydride siloxane dimethyl siloxane copolymer, GELEST HMS301).

Step 3. Rapidly Cross-Linkable Silicone Composition Preparation:

0.5 g, 1.0 g, 2.0 g, and 3.0 g of the catalyst fluid of step 1, wasadded to a respective cross-linker fluid composition of Step 2, andstirred vigorously for 1 minute, to produce test compositions 1-4, eachhaving a different platinum content, respectively, as set forth in Table1 below.

TABLE 1 Catalyst content of four one-part RCS compositions Test Testcomposition Pt Amount of catalysts Composition content solution added(g) 1 1 ppm 0.5 2 2 ppm 1.0 3 4 ppm 2.0 4 6 ppm 3.0

The viscosity of the resulting formulations was measured by a Brookfieldviscometer over a period of 30 minutes. Measurements were performedevery minute and the results are summarized in Table 2, below.

TABLE 2 Viscosity (cPs) of RCS compositions having different Pt contentover time Viscosity Viscosity Viscosity Viscosity RCS RCS RCS RCS Timecomposition 1 composition 2 composition 3 composition 4 (min) (cPs)(cPs) (cPs) (cPs) 2 100 100 110 120 3 100 107 140 165 4 100 123 190 2355 100 142 260 325 6 105 166 340 435 7 115 196 440 560 8 120 227 545 6909 135 257 660 820 10 145 296 780 950 11 150 338 905 1075 12 160 383 101013 175 435 14 190 483 15 200 535 16 215 580 17 230 630 18 245 690 19 260750 20 280 800 21 290 860 22 310 930 23 330 970 24 345 1025 25 365 26375 27 395 28 415 29 435 30 455

The curing of the RCS test compositions is shown by monitoring viscosityof the mixtures. Higher Pt content resulted in a faster increase ofviscosity. All mixtures completely stopped flowing after 2 hours.

Example 2: Preparation and of Pre-Mixed Formulation of a RapidlyCross-Linkable Silicone Composition with Variable Cross-Linker Content

The formulation of this Example includes a cross-linker content 10 timesthat of Example 1. The mixtures of this example also remained lowviscosity up to 5 minutes post-mixing, and were easily flowable througha hypodermic needle after mixing, despite the increased cross-linkercontent as compared to Example 1. The preparation of the composition wasas follows:

Step 1. Catalyst Fluid Preparation:

1 g of Karstedt catalyst (Platinum divinyl disiloxane complex, GELESTSIP 6831.2) containing 2% Pt[(CH₂═CH)(CH₃)₂SiOSi(CH₃)₂(CH═CH₂)]₃ inxylene, was mixed with 99 g of low viscosity (100 cPs) vinyl terminatedpolydimethylsiloxane (GELEST DMS V21) for 5 minutes at ambienttemperature to obtain a homogeneous solution.

Step 2. Cross-Linker Fluid Preparation:

For each of test compositions 5-7 set forth in Table 3 below, 60 g oflow viscosity vinyl terminated polydimethylsiloxane (GELEST DMS V21) wasmixed with 40 g of low viscosity hydride terminated polydimethylsiloxane(GELEST DMS H21), and 1.6 g cross linker (methylhydride siloxanedimethyl siloxane copolymer, GELEST HMS301).

Step 3. Rapidly Cross-Linkable Silicone Composition Preparation

0.5, 1.0, and 3.0 g of the catalyst fluid of step 1, was added to arespective cross-linker fluid composition of step 2, and stirredvigorously for 1 minute, to produce the present injectable testcompositions 5-7, respectively, as set forth in Table 3 below.

TABLE 3 Catalyst content of three one-part RCS compositions Test Testcomposition Pt Amount of catalysts Composition content solution added(g) 5 1 ppm 0.5 6 2 ppm 1.0 7 6 ppm 3.0

The viscosity of the resulting test compositions was measured by aBrookfield viscometer over a period of 30 minutes. Measurements wereperformed every minute and the results are summarized in Table 4, below.

TABLE 4 Viscosity (cPs) of RCS compositions having different Pt contentover time Viscosity Viscosity Viscosity RCS RCS RCS Time composition 5composition 6 composition 7 (min) (cPs) (cPs) (cPs) 2 100 100 100 3 100105 140 4 100 115 174 5 105 124 213 6 105 134 269 7 115 144 351 8 115155 524 9 120 168 865 10 125 183 1487 11 130 198 12 140 216 13 145 23714 150 258 15 160 285 16 165 315 17 175 350 18 180 402 19 190 435 20 200537 21 210 635 22 220 910 23 230 1168 24 240 25 255 26 280 27 320 28 32529 330 30 350

The curing of the present RCS compositions is shown by monitoringviscosity of the mixtures. Higher Pt content resulted in faster increaseof viscosity. All mixtures completely stopped flowing after 1 hour.

The viscosities of the fully cured systems were over 50,000 cPs andbeyond the measurement limit of the equipment.

Example 3: Injection of Rapidly Cross-Linkable Silicone Composition intoImplant

A standard cured silicone gel filled implant (MENTOR, Johnson & Johnson,N.J.) was injected with the inventive composition of Example 1,containing 4 ppm Pt, immediately after mixing the composition using asyringe with an 18 gauge needle and forming a bolus of RCS compositioninside the already cross-linked gel of the implant.

It was observed that the bolus formed a homogenous invisible and curedsilicone mass inside the implant. No leakage of injected siliconecomposition was observed. Full curing of the injected siliconecomposition was observed within less than 24 hours at ambienttemperature.

Example 4: Preparation and of Two-Part Formulations of a RapidlyCross-Linkable Silicone Composition

A catalyst component fluid and a cross-linkable silicone component fluidwere prepared and stored separately. The two components were injected asa two-part system through a mixing Y-connector with static mixersdirectly into conventional gel implants. The dual syringe used wasequipped with a direct thread static mixer and manufactured by Plas-PakIndustries, Inc, Norwich, Conn.

The catalyst component fluid was prepared by mixing 37.7 g of lowviscosity vinyl terminated polydimethylsiloxane (GELEST DMS V21) with0.6 g of catalyst (described in Example 1, above, i.e., 2% catalyst inxylene) for 5 minutes.

The cross-linkable silicone component fluid was prepared by mixing 7.3 gof low viscosity vinyl terminated polydimethylsiloxane (GELEST DMS V21)with 30 g of low viscosity hydride terminated polydimethylsiloxane(GELEST DMS H21), 0.12 g cross linker (methylhydride siloxane dimethylsiloxane copolymer, GELEST HMS301) for 5 minutes.

The catalyst component and the cross-linkable silicone component fluids,each contained in a separate syringe, were injected together through amixing Y-connector equipped with a static mixer terminating with an 18gauge hypodermic needle. The injection was directly into the siliconegel filled implant. The resulting enlarged breast implant appearshomogeneous and consistent throughout on its physical properties. Nolumps observed in the injectable portion of the implant.

Example 5: Testing RCS Formulations of Various Viscosities for InjectingThrough Hypodermic Needles of Different Gauges

Formulations 8-11 having various standard viscosities were analyzed andinjectability through needles of several sizes was assessed.

The silicone viscosity standard fluids were purchased from BrookfieldEngineering Laboratories Inc, Middleboro Mass.

TABLE 5 Assessment of injections through various gauge needles ofsilicone viscosity standard fluids having different viscosities TestViscosity of Needle gauge 15 Needle gauge 18 Needle gauge 21 Compositionstandard fluid (largest) (intermediate) (smallest) 8 ViscosityComposition passes Composition passes Composition 100 cPs through byhand through by hand passes through by operated syringe operated syringehand operated syringe 9 Viscosity Composition passes Composition passesComposition 200 cPs through by hand through by hand passes through byoperated syringe operated syringe hand operated syringe 10 ViscosityComposition passes Composition passes Some difficulty in 300 cPs throughby hand through by hand passing operated syringe operated syringecomposition through by hand operated syringe 11 Viscosity Compositionpasses Some difficulty in Composition does 500 cPs through by handpassing composition not pass through operated syringe through by hand byhand operated operated syringe syringe

This Example illustrates that all of the present RCS formulations shownin Examples 1-2 are injectable, even through the smallest, i.e., 21gauge needles, with workable shelf life of 5 minutes, having viscositiesless than or about equal to ˜300 cPs.

Example 6: Preparation of Rapidly Cross-Linkable Silicone FoamComposition

An RCS test composition 6, of Example 2, was used to form a RCSFformulation by introducing air into the liquid RCS composition. The RCScomposition 6 was prepared according to Example 2 Immediately aftermixing the catalyst fluid and the cross-linker fluid, sterile air wasbubbled, via a narrow cannnula (or a tube could be used) into the mixedliquid RCS composition, thereby forming a foam.

It is observed that while bubbling air into the RCS compositionimmediately after mixing where the RCS composition was still veryflowable, foam formation was observed; however, it was also observedthat because the viscosity of the RCS composition immediately aftermixing was low, e.g., ≤150 cPs, gas escaped for the RCS low viscositycomposition.

To prevent gas from escaping from the RCS liquid composition during orafter bubbling a gas into the composition, one or more of the followingcan be performed: bubbling can commence during or immediatelypost-mixing and can be carried out at least until the RCS bubbled liquidbegins to gel or gels, and optionally for a time sufficient to produce adesired volume of microbubbles; or bubbling can commence after the RCSmixed liquid begins to gel or gels, and optionally can be carried outfor a time sufficient to produce a desired volume of microbubbles.

When gas is bubbled into the RCS composition as the RCS compositionbegins to cross-link and gel, e.g., at or after about 1 min., about 1.5min., about 2 min., about 2.5 min., about 3 min., about 3.5 min., about4 min., or about 5 min post-mixing, and while the RCS composition isstill injectable through, for example, an 18-21 gauge needle, the gasbubbles became entrapped in the silicone matrix, and the rapidlycross-linkable silicone foam forms. Once the foam is formed or begins toform, it can then be immediately injected, for example, via an injectiondevice.

The bulk density of the formed cured foam was about 0.50 g/cm3, whilethe density of the RCS itself when cured is about 0.97 g/cm3. Thus thebulk density of the foam was about one half of the density of thesilicone.

Example 7: Preparation of Rapidly Cross-Linkable Silicone FoamComposition

An RCS composition is formed and immediately is mixed with polyethylenemicrospheres having a diameter of about 45-53 microns CPMS-0.96 fromCOSPHERIC in the amount of 20% vol/vol of microspheres, whereby ahomogeneous RCSF is formed.

Upon mixing for 1 min., the resulting flowable suspension is immediatelyinjected into an implanted medical device using appropriate gaugeneedle, such as 18-21, for example, an 18 gauge needle.

The bulk densities of the RCSF compositions are a fraction of the RCSdensity, such as from about 0.9 of RCS density to about 0.5 of thedensity of the RCS, including for example, 0.9, 0.8. 0.75, 0.6 of theRCS density, or as otherwise described herein.

The following claims particularly point out certain combinations andsubcombinations that are directed to an aspect of the presentlydescribed subject matter and are novel and non-obvious. Subject matterembodied in other combinations and subcombinations of features,functions, elements and/or properties may be claimed through amendmentof the present claims or presentation of new claims in this or a relatedapplication.

1. A two-part, rapidly cross-linkable silicone foam composition,comprising: a catalyst fluid comprising a first low viscosity vinylterminated polydimethylsiloxane present in an amount of from about 97 wt% to about 99.5 wt % based on the weight of the catalyst fluid andhaving a viscosity of from about 1 to about 150 cPs, and a platinumdivinyl disiloxane complex comprisingPt[(CH₂═CH)(CH₃)₂SiOSi(CH₃)₂(CH═CH₂)]₃ having a platinum content of fromabout 2 ppm to about 32 ppm based on the catalyst fluid, wherein thecatalyst fluid has a viscosity of from about 1 to about 150; and across-linker suspension comprising a second low viscosity vinylterminated polydimethylsiloxane present in an amount of from about 1 wt% to about 40 wt % based on the weight of the cross-linker fluid andhaving a viscosity of from about 1 to about 150 cPs, a low viscosityhydride terminated polydimethylsiloxane present in an amount of fromabout 60 wt % to about 90 wt % based on the weight of the cross-linkerfluid and having a viscosity of from about 1 to about 150 cPs, asilicone cross-linker comprising polymethylhydrosiloxanepolydimethylsiloxane copolymer present in an amount of from about 0.32wt % to about 5.0 wt % based on the weight of the cross-linker fluid,and having a viscosity of from about 1 to about 150 cPs, and a sterilegas or a population of gas-filled microcapsules, wherein thecross-linker fluid has a viscosity of from about 1 to about 150 cPs, andwherein post-preparation, the resultant rapidly cross-linkable siliconefoam composition has a viscosity of ≤150 cPs for ≥1 min.post-preparation and ≤300 cPs≤5 min. post-preparation, at ambienttemperature, and the resultant rapidly cross-linkable silicone foamcomposition has a platinum content of from about 1 ppm to about 16 ppm.2. The rapidly cross-linkable silicone foam composition of claim 1,wherein the cross-linker suspension comprises gas-filled microcapsules.3. A kit, comprising: the two-part, rapidly cross-linkable silicone foamcomposition of claim 2; a first container comprising the catalyst fluid;and a second container comprising the cross-linker suspension.
 4. Thekit of claim 3, further comprising: an injection device comprising an 18to 21 gauge hypodermic needle, the first container, and the secondcontainer, and the injection device is configured to mix and inject thecatalyst fluid and the cross-linker suspension substantiallysimultaneously at point of use, wherein the catalyst fluid and thecross-linker suspension are not in physical or reactive contact in theinjection device; and optionally, instructions for use.
 5. The kit ofclaim 4, wherein the injection device comprises: a dual syringehypodermic device comprising a connector and optionally a static mixer,wherein the first container is a first syringe of the dual syringehypodermic device, and the second container is a second syringe of thedual syringe hypodermic device; or a dual bore hypodermic deviceoptionally comprising a static mixer, wherein the first container is afirst bore of the dual bore hypodermic device, and the second containeris a second bore, separate from the first bore, of the dual borehypodermic device; or a dual chamber hypodermic syringe, wherein thefirst container comprises a first chamber in the dual chamber hypodermicsyringe, and the second container comprises a second chamber in the dualchambered syringe, wherein the first and second chambers are notcontiguous and the catalyst fluid and the cross-linker fluid are not incontact and cannot react until point of use, wherein, the first andsecond chamber are both present in a single syringe, wherein theinjection device comprises an 18 to 21 gauge hypodermic needle.
 6. Thetwo-part, rapidly cross-linkable silicone foam composition of claim 1,wherein the first low viscosity vinyl terminated polydimethylsiloxane ispresent in an amount of from about 98 wt % to about 99 wt %, theplatinum content is from about 2 to about 8 ppm, the second lowviscosity vinyl terminated polydimethylsiloxane is present in an amountof from about 15 wt % to about 25 wt %, the low viscosity hydrideterminated polydimethylsiloxane is present in an amount of from about 75wt % to about 85 wt %, and the cross-linker is present in an amount offrom about 0.25 wt % to about 2 wt %.
 7. A method of filling animplanted medical device in situ, comprising: providing the rapidlycross-linkable silicone foam composition of claim 2; mixing the catalystfluid with the cross-linker suspension to produce an injectablecomposition having an initial viscosity of <150 cPs for at least about 1min.; and within ≤5 min. of initiating mixing, and substantiallysimultaneous with mixing, injecting a predetermined volume of theinjectable composition into the implanted medical device in situ,whereby the rapidly cross-linkable silicone foam compositionsubstantially cross-links and gels in situ in an amount of time ≥5 min.to produce a filled implanted medical device comprising rapidlycross-linkable silicone foam gel, wherein the rapidly cross-linkablesilicone foam gel has a viscosity ≥50,000 cPs≤24 hrs. post-injection atambient temperature.
 8. The method of claim 7, wherein the implantedmedical device comprises silicone.
 9. The method of claim 7, wherein thefilled implanted medical device is free from any physical defect. 10.The method of claim 7, wherein post-injection, there is no leakage ofthe silicone foam gel from the filled implanted medical device at theinjection site.
 11. The method of claim 7, wherein the implanted medicaldevice comprises a breast implant, an adjustable breast implant, a calfimplant, a tissue expander, or a lumpectomy implant.
 12. The method ofclaim 11, wherein the implanted medical device comprises: at least oneempty envelope, and injecting comprises injecting into the emptyenvelope; and/or at least one silicone containing envelope, andinjecting comprises injecting into the silicone containing envelope. 13.The method of claim 12, wherein the implanted medical device comprisesan implanted silicone breast implant comprising the at least onesilicone containing envelope, and the predetermined volume of theinjectable composition comprises a volume of from about 50 ml to about800 ml.
 14. The method of claim 11, wherein the implanted medical devicecomprises an unfilled tissue expander or an unfilled lumpectomy implant.15. The method of claim 11, wherein the implanted medical devicecomprises an adjustable breast implant comprising an unfilled firstenvelope and a second envelope comprising a silicone gel.
 16. The methodof claim 15, wherein injecting comprises injecting the volume into thefirst unfilled envelope and/or the second envelope.
 17. The method ofclaim 11, wherein the implanted medical device comprises a siliconefilled breast implant comprising a shell having an upper pole wrinklingdefect and/or lower pole wrinkling defect.
 18. The method of claim 17,wherein injecting comprises injecting a volume of the rapidlycross-linkable silicone foam composition into the upper pole and/or thelower pole of the shell at a site of wrinkling, wherein the volume issufficient to fill the shell to capacity, whereby the wrinkling defectis ameliorated or eliminated.
 19. A method of adjusting the volume of animplanted medical device in situ, comprising: providing the kit of claim5, wherein the injection device comprises the dual syringe hypodermicdevice; mixing the catalyst fluid with the cross-linker suspension viathe static mixer to produce an injectable composition having an initialviscosity of <150 cPs for at least about 1 min.; and within ≤5 min. ofinitiating mixing, and substantially simultaneous with mixing, injectinga predetermined volume of the injectable composition via the injectiondevice, into the implanted medical device in situ, whereby the rapidlycross-linkable silicone foam composition substantially cross-links andgels in situ in an amount of time ≥5 min. to produce a filled implantedmedical device comprising the silicone foam gel, wherein the rapidlycross-linkable silicone foam gel has a viscosity ≥50,000 cPs≤24 hrs.post-injection at ambient temperature, and the volume of the implanteddevice has been adjusted.
 20. The method of claim 19, wherein theimplanted device comprises an adjustable breast implant comprising anunfilled first envelope and a second envelope comprising a silicone gel,and injecting comprises injecting the volume into the first unfilledenvelope and/or the second envelope.